Intraarticular etanercept attenuates pain and hypoxia from TMJ loading in the rat
| Autor: | Rachel L. Welch, Beth A. Winkelstein, Ya-Hsin Yu, Prabesh Ghimire, Megan M. Sperry, Sonia Kartha, Eric J. Granquist |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Hydrocarbons Fluorinated 0206 medical engineering Inflammation 02 engineering and technology Osteoarthritis Article Etanercept Injections Intra-Articular Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Basic Helix-Loop-Helix Transcription Factors Animals Pain Management Orthopedics and Sports Medicine Etanidazole Hypoxia 030203 arthritis & rheumatology Temporomandibular Joint business.industry Tumor Necrosis Factor-alpha Cartilage Hypoxia (medical) medicine.disease 020601 biomedical engineering Temporomandibular joint Rats stomatognathic diseases Endocrinology medicine.anatomical_structure Immunohistochemistry Tumor necrosis factor alpha Female medicine.symptom business medicine.drug |
| Zdroj: | J Orthop Res |
| Popis: | Mechanical overloading of the temporomandibular joint (TMJ) and biochemical changes, like inflammation and hypoxia, contribute to cartilage degeneration and pain associated with osteoarthritis (OA). Yet, how overloading contributes to early dysregulation of chondrocytes is not understood, limiting the development of diagnostics and treatments for TMJ OA. Hypoxia-inducible factors (HIF)-1α/2α in chondrocytes were evaluated at Days 8 and 15 in a rat TMJ pain model induced by jaw loading (1 h/day for 7 days) using immunohistochemistry and compared between cases that induce persistent (3.5 N), acute (2 N), or no (0 N) sensitivity. Hypoxia was measured on Day 8 by immunolabeling of the tracer EF5 and 18 F-EF5 PET imaging. To assess the role of tumor necrosis factor (TNF) in painful TMJ loading, intra-articular etanercept was given before loading. Orofacial sensitivity was evaluated during and after loading. Facial grimace, TNF-α, HIF-2α, and hypoxia levels in the TMJ were measured after loading. HIF-2α was elevated (P = .03) after 3.5 N loading at Day 8, but HIF-1α was unchanged. EF5 uptake increased on Day 8 in the 3.5 N group (P < .048) by tissue assay and 18 F-EF5 PET. At Day 8, both HIF-2α (P = .01) and EF5 uptake (P = .005) were correlated with loading magnitude. Etanercept attenuated sensitivity (P < .01) and the facial grimace on Day 7 (P = .01). It also reduced (P < .01) HIF-2α and EF5 uptake on Day 8; but TNF-α levels were not different from controls at that time. Findings suggest that TMJ loading that induces persistent sensitivity upregulates the catabolic factor HIF-2α and reduces oxygen levels in the cartilage, which may be TNF-driven. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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